TRAIL promotes membrane blebbing, detachment and migration of cells displaying a dysfunctional intrinsic pathway of apoptosis.
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| Abstract |
Recently, tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL/Apo2L) has been shown to be a potential candidate for cancer therapy. TRAIL induces apoptosis in various cancer cells but not in normal tissues. Here we show that HCT116 and SW480 cells with a deficient mitochondrial apoptotic pathway were resistant to TRAIL-induced apoptosis, whereas HCT116 and SW480 cells with a functional mitochondrial apoptotic pathway underwent apoptosis upon exposure to TRAIL. Surprisingly, TRAIL induced phenotypic changes in cells with a dysfunctional mitochondrial apoptotic pathway, including membrane blebbing and a transient loss of adhesion properties to the substratum. Accordingly, TRAIL stimulated the ability of these cells to migrate. This behavior was the consequence of a transient TRAIL-induced ROCK1 cleavage. In addition, we report that Bax-deficient HCT116 cells exposed to TRAIL for a prolonged period lost their sensitivity to TRAIL as a result of downregulation of TRAIL receptor expression, and became resistant to combination of TRAIL and other drugs such as MG-132 and bortezomib. These findings may have important consequences for TRAIL anti-cancer therapy.
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| Authors | Syam Prakash Somasekharan, Michal Koc, Alexandre Morizot, Olivier Micheau, Poul H B Sorensen, Olivier Gaide, Ladislav Andera, Jean-Claude Martinou |
| Journal | Apoptosis : an international journal on programmed cell death (Apoptosis) Vol. 18 Issue 3 Pg. 324-36 (Mar 2013) ISSN: 1573-675X [Electronic] Netherlands |
| PMID | 23179179 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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